Combination Of Anti-RANTES With Cyclosporine A For Induction Of Long-term Immune Tolerance In Heart Retransplantation Of Mice

Objective: To Explore the function and mechanism of combination of Anti-RANTES with Cyclosporine A for induction of long-term immune tolerance in heart retransplantation of mice.Methods: Building experimental model of heart retransplantation in mice. In the retransplantation model, hearts from BALB/c mice were maidenly transplanted into C57BL/6 recipients via abdominal route. Two weeks after maiden heart transplantation, hearts from BALB/c mice were transplanted into viable C57BL/6 recipients via cervical route. Then they were administrated with sodium chloride dissolvant, single use of Anti-RANTES, single use of Cyclosporine A and associated use of them, marked as control group, experimental group A, experimental group B and experimental group C, respectively(n=6). Animals were sacrificed when the transplanted hearts stopped beating. In the retransplantation model, the survival time of transplanted hearts was recorded,and immune rejection levels in allografts were analyzed by histopathological change of HE dyed slices. The gene expression and serum concentration levels of RANTES 、INF-γ、IL-2、IL-10 and TGF-β were assessed by Q-PCR and ELISA method.Results: The mean graft survival time was 8.58 days in the experimental group C(n=6), as compared with 3.1 days in the control group(n=6; P<0.001). On day three following cardiac retransplantation, histologicalevaluation of the grafts revealed a higher International Society for Heart & Lung Transplantation grade in the control group as compared with the experimental group. In addition, gene expression and serum concentrations of RANTES, interferon- γ, and interleukin-2 were markedly higher in the control group when compared with the experimental group.Conclusions: Differences levels of cytokines during the control and experimental groups demonstrated that CC motif chemokine ligand(CCL)5 and various cytokines play key roles in the initiation and development of acute transplant rejection. Anti-RANTES in combination with Cyclosporine A is effective in prolonging allograft survival time and protecting cardiac allograft by reducing the migration of inflammation cells to grafts, reducing the secretion and infiltration of inflammatory cytokines such as INF-γand IL-2 while increasing the secretion of anti-inflammatory cytokines such as IL-10 and TGF- β in a retransplantation murine model.